{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:18:11Z","timestamp":1791353891588,"version":"4.3.1"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,8,31]],"date-time":"2016-08-31T00:00:00Z","timestamp":1472601600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,8,31]],"date-time":"2016-08-31T00:00:00Z","timestamp":1472601600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The multidrug resistance <jats:italic>Salmonella<\/jats:italic> Genomic Island 1 (SGI1) is an integrative mobilizable element identified in several enterobacterial pathogens. This chromosomal island requires a conjugative IncA\/C plasmid to be excised as a circular extrachromosomal form and conjugally mobilized <jats:italic>in trans<\/jats:italic>. Preliminary observations suggest stable maintenance of SGI1 in the host chromosome but paradoxically also incompatibility between SGI1 and IncA\/C plasmids. Here, using a <jats:italic>Salmonella enterica<\/jats:italic> serovar Agona clonal bacterial population as model, we demonstrate that a Toxin-Antitoxin (TA) system encoded by SGI1 plays a critical role in its stable host maintenance when an IncA\/C plasmid is concomitantly present. This system, designated <jats:italic>sgiAT<\/jats:italic> for <jats:italic>Salmonella<\/jats:italic> genomic island 1 Antitoxin and Toxin respectively, thus seems to play a stabilizing role in a situation where SGI1 is susceptible to be lost through plasmid IncA\/C-mediated excision. Moreover and for the first time, the incompatibility between SGI1 and IncA\/C plasmids was experimentally confirmed.<\/jats:p>","DOI":"10.1038\/srep32285","type":"journal-article","created":{"date-parts":[[2016,8,31]],"date-time":"2016-08-31T16:53:45Z","timestamp":1472662425000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["A toxin antitoxin system promotes the maintenance of the IncA\/C-mobilizable Salmonella Genomic Island 1"],"prefix":"10.1038","volume":"6","author":[{"given":"Kevin T.","family":"Huguet","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathieu","family":"Gonnet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beno\u00eet","family":"Doublet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Cloeckaert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,8,31]]},"reference":[{"key":"BFsrep32285_CR1","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1111\/j.1574-6968.2000.tb09245.x","volume":"189","author":"DA Boyd","year":"2000","unstructured":"Boyd, D. A., Peters, G. A., Ng, L. & Mulvey, M. R. Partial characterization of a genomic island associated with the multidrug resistance region of Salmonella enterica Typhymurium DT104. FEMS Microbiol Lett 189, 285\u2013291 (2000).","journal-title":"FEMS Microbiol Lett"},{"key":"BFsrep32285_CR2","doi-asserted-by":"publisher","first-page":"5725","DOI":"10.1128\/JB.183.19.5725-5732.2001","volume":"183","author":"D Boyd","year":"2001","unstructured":"Boyd, D. et al. Complete nucleotide sequence of a 43-kilobase genomic island associated with the multidrug resistance region of Salmonella enterica serovar Typhimurium DT104 and its identification in phage type DT120 and serovar Agona. J Bacteriol 183, 5725\u20135732 (2001).","journal-title":"J Bacteriol"},{"key":"BFsrep32285_CR3","doi-asserted-by":"publisher","first-page":"1915","DOI":"10.1016\/j.micinf.2005.12.028","volume":"8","author":"MR Mulvey","year":"2006","unstructured":"Mulvey, M. R., Boyd, D. A., Olson, A. B., Doublet, B. & Cloeckaert, A. The genetics of Salmonella genomic island 1. Microbes Infect 8, 1915\u20131922 (2006).","journal-title":"Microbes Infect"},{"key":"BFsrep32285_CR4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/2159256X.2015.1006109","volume":"5","author":"N Carraro","year":"2015","unstructured":"Carraro, N., Matteau, D., Burrus, V. & Rodrigue, S. Unraveling the regulatory network of IncA\/C plasmid mobilization: When genomic islands hijack conjugative elements. Mob Genet Elements 5, 1\u20135 (2015).","journal-title":"Mob Genet Elements"},{"key":"BFsrep32285_CR5","doi-asserted-by":"publisher","first-page":"e1004714","DOI":"10.1371\/journal.pgen.1004714","volume":"10","author":"N Carraro","year":"2014","unstructured":"Carraro, N., Matteau, D., Luo, P., Rodrigue, S. & Burrus, V. The master activator of IncA\/C conjugative plasmids stimulates genomic islands and multidrug resistance dissemination. PLoS Genet 10, e1004714 (2014).","journal-title":"PLoS Genet"},{"key":"BFsrep32285_CR6","doi-asserted-by":"publisher","first-page":"1911","DOI":"10.1111\/j.1365-2958.2005.04520.x","volume":"55","author":"B Doublet","year":"2005","unstructured":"Doublet, B., Boyd, D., Mulvey, M. R. & Cloeckaert, A. The Salmonella genomic island 1 is an integrative mobilizable element. Mol Microbiol 55, 1911\u20131924 (2005).","journal-title":"Mol Microbiol"},{"key":"BFsrep32285_CR7","doi-asserted-by":"publisher","first-page":"e32497","DOI":"10.1371\/journal.pone.0032497","volume":"7","author":"J Kiss","year":"2012","unstructured":"Kiss, J., Nagy, B. & Olasz, F. Stability, entrapment and variant formation of Salmonella genomic island 1. PLoS One 7, e32497 (2012).","journal-title":"PLoS One"},{"key":"BFsrep32285_CR8","doi-asserted-by":"publisher","first-page":"8735","DOI":"10.1093\/nar\/gkv758","volume":"43","author":"J Kiss","year":"2015","unstructured":"Kiss, J. et al. The master regulator of IncA\/C plasmids is recognized by the Salmonella Genomic island SGI1 as a signal for excision and conjugal transfer. Nucleic Acids Res 43, 8735\u20138745 (2015).","journal-title":"Nucleic Acids Res"},{"key":"BFsrep32285_CR9","doi-asserted-by":"publisher","first-page":"e15302","DOI":"10.1371\/journal.pone.0015302","volume":"5","author":"G Douard","year":"2010","unstructured":"Douard, G., Praud, K., Cloeckaert, A. & Doublet, B. The Salmonella genomic island 1 is specifically mobilized in trans by the IncA\/C multidrug resistance plasmid family. PLoS One 5, e15302 (2010).","journal-title":"PLoS One"},{"key":"BFsrep32285_CR10","doi-asserted-by":"publisher","first-page":"837","DOI":"10.3389\/fmicb.2015.00837","volume":"6","author":"D Poulin-Laprade","year":"2015","unstructured":"Poulin-Laprade, D., Carraro, N. & Burrus, V. The extended regulatory networks of SXT\/R391 integrative and conjugative elements and IncA\/C conjugative plasmids. Front Microbiol 6, 837 (2015).","journal-title":"Front Microbiol"},{"key":"BFsrep32285_CR11","doi-asserted-by":"publisher","first-page":"4401","DOI":"10.1128\/JB.187.13.4401-4409.2005","volume":"187","author":"RS Levings","year":"2005","unstructured":"Levings, R. S., Lightfoot, D., Partridge, S. R., Hall, R. M. & Djordjevic, S. P. The genomic island SGI1, containing the multiple antibiotic resistance region of Salmonella enterica serovar Typhimurium DT104 or variants of it, is widely distributed in other S. enterica serovars. J Bacteriol 187, 4401\u20134409 (2005).","journal-title":"J Bacteriol"},{"key":"BFsrep32285_CR12","doi-asserted-by":"publisher","first-page":"6601","DOI":"10.1128\/AAC.00292-15","volume":"59","author":"S Qin","year":"2015","unstructured":"Qin, S. et al. Emergence of extensively drug-resistant Proteus mirabilis harboring a conjugative NDM-1 plasmid and a novel Salmonella genomic island 1 variant, SGI1-Z. Antimicrob Agents Chemother 59, 6601\u20136604 (2015).","journal-title":"Antimicrob Agents Chemother"},{"key":"BFsrep32285_CR13","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1093\/jac\/dkl471","volume":"59","author":"AM Ahmed","year":"2007","unstructured":"Ahmed, A. M., Hussein, A. I. & Shimamoto, T. Proteus mirabilis clinical isolate harbouring a new variant of Salmonella genomic island 1 containing the multiple antibiotic resistance region. J Antimicrob Chemother 59, 184\u2013190 (2007).","journal-title":"J Antimicrob Chemother"},{"key":"BFsrep32285_CR14","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1128\/AAC.00902-07","volume":"52","author":"DA Boyd","year":"2008","unstructured":"Boyd, D. A. et al. Salmonella genomic island 1 (SGI1), variant SGI1-I, and new variant SGI1-O in Proteus mirabilis clinical and food isolates from China. Antimicrob Agents Chemother 52, 340\u2013344 (2008).","journal-title":"Antimicrob Agents Chemother"},{"key":"BFsrep32285_CR15","doi-asserted-by":"publisher","first-page":"2513","DOI":"10.1093\/jac\/dkr335","volume":"66","author":"E Siebor","year":"2011","unstructured":"Siebor, E. & Neuwirth, C. The new variant of Salmonella genomic island 1 (SGI1-V) from a Proteus mirabilis French clinical isolate harbours bla VEB-6 and qnrA1 in the multiple antibiotic resistance region. J Antimicrob Chemother 66, 2513\u20132520 (2011).","journal-title":"J Antimicrob Chemother"},{"key":"BFsrep32285_CR16","doi-asserted-by":"publisher","first-page":"1750","DOI":"10.1093\/jac\/dkt100","volume":"68","author":"E Siebor","year":"2013","unstructured":"Siebor, E. & Neuwirth, C. Emergence of Salmonella genomic island 1 (SGI1) among Proteus mirabilis clinical isolates in Dijon, France. J Antimicrob Chemother 68, 1750\u20131756 (2013).","journal-title":"J Antimicrob Chemother"},{"key":"BFsrep32285_CR17","doi-asserted-by":"publisher","first-page":"3216","DOI":"10.1093\/jac\/dku314","volume":"69","author":"E Siebor","year":"2014","unstructured":"Siebor, E. & Neuwirth, C. Proteus genomic island 1 (PGI1), a new resistance genomic island from two Proteus mirabilis French clinical isolates. J Antimicrob Chemother 69, 3216\u20133220 (2014).","journal-title":"J Antimicrob Chemother"},{"key":"BFsrep32285_CR18","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1093\/jac\/dku371","volume":"70","author":"D Girlich","year":"2015","unstructured":"Girlich, D., Dortet, L., Poirel, L. & Nordmann, P. Integration of the bla NDM-1 carbapenemase gene into Proteus genomic island 1 (PGI1-PmPEL) in a Proteus mirabilis clinical isolate. J Antimicrob Chemother 70, 98\u2013102 (2015).","journal-title":"J Antimicrob Chemother"},{"key":"BFsrep32285_CR19","doi-asserted-by":"publisher","first-page":"2543","DOI":"10.1093\/jac\/dkv154","volume":"70","author":"E Schultz","year":"2015","unstructured":"Schultz, E. et al. Survey of multidrug resistance integrative mobilizable elements SGI1 and PGI1 in Proteus mirabilis in humans and dogs in France, 2010\u201313. J Antimicrob Chemother 70, 2543\u20132546 (2015).","journal-title":"J Antimicrob Chemother"},{"key":"BFsrep32285_CR20","doi-asserted-by":"publisher","first-page":"304","DOI":"10.3390\/toxins6010304","volume":"6","author":"N Goeders","year":"2014","unstructured":"Goeders, N. & Van Melderen, L. Toxin-antitoxin systems as multilevel interaction systems. Toxins (Basel) 6, 304\u2013324 (2014).","journal-title":"Toxins (Basel)"},{"key":"BFsrep32285_CR21","doi-asserted-by":"publisher","first-page":"283","DOI":"10.4161\/mge.18477","volume":"1","author":"J Guglielmini","year":"2011","unstructured":"Guglielmini, J. & Van Melderen, L. Bacterial toxin-antitoxin systems: Translation inhibitors everywhere. Mob Genet Elements 1, 283\u2013290 (2011).","journal-title":"Mob Genet Elements"},{"key":"BFsrep32285_CR22","doi-asserted-by":"publisher","first-page":"386","DOI":"10.3109\/10409238.2011.600437","volume":"46","author":"F Hayes","year":"2011","unstructured":"Hayes, F. & Van Melderen, L. Toxins-antitoxins: diversity, evolution and function. Crit Rev Biochem Mol Biol 46, 386\u2013408 (2011).","journal-title":"Crit Rev Biochem Mol Biol"},{"key":"BFsrep32285_CR23","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1016\/j.mib.2010.10.006","volume":"13","author":"L Van Melderen","year":"2010","unstructured":"Van Melderen, L. Toxin\u2013antitoxin systems: why so many, what for? Curr Opin Microbiol 13, 781\u2013785 (2010).","journal-title":"Curr Opin Microbiol"},{"key":"BFsrep32285_CR24","doi-asserted-by":"publisher","first-page":"e1000437","DOI":"10.1371\/journal.pgen.1000437","volume":"5","author":"L Van Melderen","year":"2009","unstructured":"Van Melderen, L. & Saavedra De Bast, M. Bacterial toxin-antitoxin systems: more than selfish entities? PLoS Genet 5, e1000437 (2009).","journal-title":"PLoS Genet"},{"key":"BFsrep32285_CR25","doi-asserted-by":"publisher","first-page":"e1005298","DOI":"10.1371\/journal.pgen.1005298","volume":"11","author":"N Carraro","year":"2015","unstructured":"Carraro, N., Poulin, D. & Burrus, V. Replication and active partition of integrative and conjugative elements (ICEs) of the SXT\/R391 family: The line between ICEs and conjugative plasmids is getting thinner. PLoS Genet 11, e1005298 (2015).","journal-title":"PLoS Genet"},{"key":"BFsrep32285_CR26","doi-asserted-by":"publisher","first-page":"e1000439","DOI":"10.1371\/journal.pgen.1000439","volume":"5","author":"RA Wozniak","year":"2009","unstructured":"Wozniak, R. A. & Waldor, M. K. A toxin-antitoxin system promotes the maintenance of an integrative conjugative element. PLoS Genet 5, e1000439 (2009).","journal-title":"PLoS Genet"},{"key":"BFsrep32285_CR27","doi-asserted-by":"publisher","first-page":"3116","DOI":"10.1073\/pnas.83.10.3116","volume":"83","author":"K Gerdes","year":"1986","unstructured":"Gerdes, K., Rasmussen, P. B. & Molin, S. Unique type of plasmid maintenance function: postsegregational killing of plasmid-free cells. Proc Natl Acad Sci USA 83, 3116\u20133120 (1986).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep32285_CR28","doi-asserted-by":"crossref","unstructured":"Hern\u00e1ndez-Arriaga, A. M., Chan, W. T., Espinosa, M. & D\u00edaz-Orejas, R. Conditional Activation of Toxin-Antitoxin Systems: Postsegregational Killing and Beyond. Microbiol Spectr 2, doi: 10.1128\/microbiolspec.PLAS-0009-2013 (2014).","DOI":"10.1128\/microbiolspec.PLAS-0009-2013"},{"key":"BFsrep32285_CR29","doi-asserted-by":"publisher","first-page":"4656","DOI":"10.1128\/JB.00124-09","volume":"191","author":"S Yamamoto","year":"2009","unstructured":"Yamamoto, S., Kiyokawa, K., Tanaka, K., Moriguchi, K. & Suzuki, K. Novel toxin-antitoxin system composed of serine protease and AAA-ATPase homologues determines the high level of stability and incompatibility of the tumor-inducing plasmid pTiC58. J Bacteriol 191, 4656\u20134666 (2009).","journal-title":"J Bacteriol"},{"key":"BFsrep32285_CR30","doi-asserted-by":"publisher","first-page":"5513","DOI":"10.1093\/nar\/gkr131","volume":"39","author":"R Leplae","year":"2011","unstructured":"Leplae, R. et al. Diversity of bacterial type II toxin\u2013antitoxin systems: a comprehensive search and functional analysis of novel families. Nucleic Acids Res 39, 5513\u20135525 (2011).","journal-title":"Nucleic Acids Res"},{"key":"BFsrep32285_CR31","doi-asserted-by":"publisher","first-page":"4603","DOI":"10.1128\/JB.00357-08","volume":"190","author":"M Saavedra De Bast","year":"2008","unstructured":"Saavedra De Bast, M., Mine, N. & Van Melderen, L. Chromosomal toxin-antitoxin systems may act as antiaddiction modules. J Bacteriol 190, 4603\u20134609 (2008).","journal-title":"J Bacteriol"},{"key":"BFsrep32285_CR32","doi-asserted-by":"publisher","first-page":"2712","DOI":"10.1128\/JB.01679-06","volume":"189","author":"M Wilbaux","year":"2007","unstructured":"Wilbaux, M., Mine, N., Gu\u00e9rout, A. M., Mazel, D. & Van Melderen, L. Functional interactions between coexisting toxin-antitoxin systems of the ccd family in Escherichia coli O157:H7. J Bacteriol 189, 2712\u20132719 (2007).","journal-title":"J Bacteriol"},{"key":"BFsrep32285_CR33","doi-asserted-by":"publisher","first-page":"1908","DOI":"10.1128\/AEM.02228-08","volume":"75","author":"RL Lindsey","year":"2009","unstructured":"Lindsey, R. L., Fedorka-Cray, P. J., Frye, J. G. & Meinersmann, R. J. Inc A\/C plasmids are prevalent in multidrug-resistant Salmonella enterica isolates. Appl. Environ. Microbiol. 75, 1908\u20131915 (2009).","journal-title":"Appl. Environ. Microbiol."},{"key":"BFsrep32285_CR34","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1093\/infdis\/jir409","volume":"204","author":"S Le Hello","year":"2011","unstructured":"Le Hello, S. et al. International spread of an epidemic population of Salmonella enterica serotype Kentucky ST198 resistant to ciprofloxacin. J Infect Dis 204, 675\u2013684 (2011).","journal-title":"J Infect Dis"},{"key":"BFsrep32285_CR35","doi-asserted-by":"publisher","first-page":"395","DOI":"10.3389\/fmicb.2013.00395","volume":"4","author":"S Le Hello","year":"2013","unstructured":"Le Hello, S. et al. The global establishment of a highly-fluoroquinolone resistant Salmonella enterica serotype Kentucky ST198 strain. Front Microbiol 4, 395 (2013).","journal-title":"Front Microbiol"},{"key":"BFsrep32285_CR36","first-page":"3405","volume":"70","author":"S Ktari","year":"2015","unstructured":"Ktari, S. et al. Carbapenemase-producing Salmonella enterica serotype Kentucky ST198, North Africa. J Antimicrob Chemother 70, 3405\u20133407 (2015).","journal-title":"J Antimicrob Chemother"},{"key":"BFsrep32285_CR37","first-page":"6126","volume":"183","author":"JE Cabrera","year":"2001","unstructured":"Cabrera, J. E. & Jin, D. J. Growth phase and growth rate regulation of the rapA gene, encoding the RNA polymerase-associated protein RapA in Escherichia coli. J Bacteriol 183, 6126\u20136134 (2001).","journal-title":"Escherichia coli. J Bacteriol"},{"key":"BFsrep32285_CR38","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1093\/genetics\/51.2.167","volume":"51","author":"N Glansdorff","year":"1965","unstructured":"Glansdorff, N. Topography of cotransducible arginine mutations in escherichia COLI K-12. Genetics 51, 167\u2013179 (1965).","journal-title":"Genetics"},{"key":"BFsrep32285_CR39","doi-asserted-by":"publisher","first-page":"4121","DOI":"10.1128\/jb.177.14.4121-4130.1995","volume":"177","author":"LM Guzman","year":"1995","unstructured":"Guzman, L. M., Belin, D., Carson, M. J. & Beckwith, J. Tight regulation, modulation, and high-level expression by vectors containing the arabinose PBAD promoter. J Bacteriol 177, 4121\u20134130 (1995).","journal-title":"J Bacteriol"},{"key":"BFsrep32285_CR40","doi-asserted-by":"publisher","first-page":"6929","DOI":"10.1073\/pnas.81.22.6929","volume":"81","author":"J Brosius","year":"1984","unstructured":"Brosius, J. & Holy, A. Regulation of ribosomal RNA promoters with a synthetic lac operator. Proc Natl Acad Sci USA 81, 6929\u20136933 (1984).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep32285_CR41","doi-asserted-by":"publisher","first-page":"6640","DOI":"10.1073\/pnas.120163297","volume":"97","author":"KA Datsenko","year":"2000","unstructured":"Datsenko, K. A. & Wanner, B. L. One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products. Proc Natl Acad Sci USA 97, 6640\u20136645 (2000).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep32285_CR42","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1016\/j.mimet.2008.06.010","volume":"75","author":"B Doublet","year":"2008","unstructured":"Doublet, B. et al. Antibiotic marker modifications of \u03bb Red and FLP helper plasmids, pKD46 and pCP20, for inactivation of chromosomal genes using PCR products in multidrug-resistant strains. J Microbiol Methods 75, 359\u2013361 (2008).","journal-title":"J Microbiol Methods"},{"key":"BFsrep32285_CR43","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1093\/protein\/1.4.327","volume":"1","author":"T Miki","year":"1987","unstructured":"Miki, T. et al. Construction of a plasmid vector for the regulatable high level expression of eukaryotic genes in Escherichia coli: an application to overproduction of chicken lysozyme. Protein Eng 1, 327\u2013332 1987.","journal-title":"Protein Eng"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep32285.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep32285","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep32285.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T06:03:20Z","timestamp":1672898600000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep32285"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,8,31]]},"references-count":43,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,8,31]]}},"alternative-id":["BFsrep32285"],"URL":"https:\/\/doi.org\/10.1038\/srep32285","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,8,31]]},"assertion":[{"value":"4 May 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 August 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 August 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"32285"}}